Molecular changes during progression from nonmuscle invasive to advanced urothelial carcinoma.

Autor: Sjödahl G; Department of Translational Medicine, Division of Urological Research, Lund University, Lund, Sweden.; Department of Urology, Skåne University Hospital, Skåne, Sweden., Eriksson P; Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden., Patschan O; Department of Translational Medicine, Division of Urological Research, Lund University, Lund, Sweden.; Department of Urology, Skåne University Hospital, Skåne, Sweden., Marzouka NA; Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden., Jakobsson L; Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden., Bernardo C; Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden., Lövgren K; Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden., Chebil G; Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden., Zwarthoff E; Department of Pathology, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, The Netherlands., Liedberg F; Department of Translational Medicine, Division of Urological Research, Lund University, Lund, Sweden.; Department of Urology, Skåne University Hospital, Skåne, Sweden., Höglund M; Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2020 May 01; Vol. 146 (9), pp. 2636-2647. Date of Electronic Publication: 2019 Nov 14.
DOI: 10.1002/ijc.32737
Abstrakt: Molecular changes occurring during invasion and clinical progression of cancer are difficult to study longitudinally in patient-derived material. A unique feature of urothelial bladder cancer (UBC) is that patients frequently develop multiple nonmuscle invasive tumors, some of which may eventually progress to invade the muscle of the bladder wall. Here, we use a cohort of 73 patients that experienced a total of 357 UBC diagnoses to study the stability or change in detected molecular alterations during cancer progression. The tumors were subtyped by gene expression profiling and analyzed for hotspot mutations in FGFR3, PIK3CA and TERT, the most frequent early driver mutations in this tumor type. TP53 alterations, frequent in advanced UBC, were inferred from p53 staining pattern, and potential genomic alterations were inferred by gene expression patterns at regions harboring frequent copy number alterations. We show that early driver mutations were largely preserved in UBC recurrences. Changes in FGFR3, PIK3CA or TERT mutation status were not linked to changes in molecular subtype and aggressive behavior. Instead, changes into a more aggressive molecular subtype seem to be associated with p53 alterations. We analyze changes in gene expression from primary tumors, to recurrences and progression tumors, and identify two modes of progression: Patients for whom progression is preceded by or coincides with a radical subtype shift, and patients who progress without any systematic molecular changes. For the latter group of patients, progression may be either stochastic or depending on factors already present at primary tumor initiation.
(© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Databáze: MEDLINE
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